
The Spinal Cord Injury Research Facility continues to make significant progress in a number of research areas to develop cures for spinal cord injury. We have a busy summer ahead with 6 summer students joining us to work on new or ongoing projects.
Blocking chronic inflammation
Based on our work showing the protective effects of using our connexin channel blocking peptide to prevent inflammation early after injury , we now believe that using a similar approach to block ongoing inflammation will reduce neuropathic pain and create an environment that allows repair to occur. With funding from the Catwalk Trust, a project is underway to test an existing drug (Tonabersat) that we have identified as a channel blocker. This drug has the advantage that is has been used in several phase two clinical trials, including long term prophylactic use for migraine prevention and is proposed as a treatment for epilepsy. We have developed an improved dosing profile and already have data for central nervous system (CNS) treatments.
Gene therapy
This project, carried out by PhD student Jarred Griffin has been eevaluating theuse of gene therapy to deliver a protein that breaks down scar tissue after injury and allows regrowth and reconnection of nerve cells and has shown some really exciting results. We know that this treatment reduces the size of the injury, reduces the amount of scarring and allows nerve cells to regrow and reconnect. We have also carried out experiments where we have used the gene therapy in conjuction with exercise rehabilitation. This rehabilitation strengthens the nerve connections to the limbs and in our experiments we have seen an even greater improvement in walking and coordination. These experiments show that combining different approaches will be the way to finding a cure and our future plans are to combine a number of the approaches we have been developing to provide the greatest benefit possible.
Protecting blood vessels
Following spinal cord injury, blood vessels are damaged and this leads to the injury becoming worse. Work by three students in the lab, Connor Clemett, Laverne Robilliard and Andrea Gu has made some important advances in understanding how blood vessels are affected by injury and how we can protect them. Andrea and Laverne’s project’s have discovered some interesting findings about how the blood vessels change with injury, which will help us design ways to regrow them after injury. Connor’s project tested compounds to strengthen the blood vessels and has made some really exciting findings about how we can protect blood vessels against the damage that occurs.
A number of new projects are also progressing well
1) Use of multielectrode arrays for guidance of nerve cells
A collaboration has been established with the School of Pharmacy, University of Auckland and the Freiburg Institute for Advanced Studies, Germany to test the use of multielectrode arrays to measure electrical changes that occur with injury and use electric currents to guide the growth of nerve cells across an injured cord. We have designed and tested a microelectrode array and can measure electrical signals in the cord. This is an important first step in being able to stimulate the cord after injury to regrow nerve cells. This technology has real potential as nerve cells could be guided to reconnect across the damaged cord, reforming connections and allowing for functional recovery.
2) Targeted drug delivery
A project is underway in collaboration with researchers from the School of Pharmacy and Department of Physiology at the University of Auckland to test ways of targeting drugs directly to the site of a spinal cord injury. This is done using small packages (called liposomes) that can be targeted directly to specific cells at the injury site, including nerve cells and scar cells. This approach has an advantage over injecting drugs directly into the blood as it means that the drug will not be broken down in the blood stream and the optimum dose can be delivered directly to the injury. It also means that the amount of drug that is needed can be reduced, which will mean that unwanted side-effects are less likely. Side effects are a major issue with some drugs being currently tested and this approach could allow smaller doses to be used, avoiding this problem. A student, Julia Newland, is testing the best time to deliver these liposomes to the injured cord. Over the summer we will test targeting drugs to scar forming cells with the next step being to test these drugs in our model of spinal cord injury.
Simon O’Carroll
(on behalf of the Spinal Cord Injury Research Facility team)